Tissue Regeneration

Newts have inspired a new technique for regenerating mammalian tissue.

Transcript

Regenerating organs. I'm Bob Hirshon and this is Science Update.

Our livers can regenerate, but it would be great if other tissues could too. Now, researchers at the Stanford University School of Medicine are a step closer to that: they've regenerated healthy, functional mouse muscle cells in the lab. The muscle cells reproduced themselves when two tumor-suppressing proteins were temporarily blocked. Biologist Helen Blau says the technique could be a simpler alternative to using all-purpose stem cells.

Blau: Because the cells know their identity. And, you get around the problem of trying to direct the cell down a pathway, when we don't know all the regulatory networks involved. Of course, those tumor-suppressing proteins have a job to do, so any therapy in humans would have to be as brief and localized as possible. I'm Bob Hirshon, for AAAS, the science society.

Making Sense of the Research

Regeneration, or the ability to replace damaged or missing body parts, generally gets rarer as organisms get more complex. Newts, salamanders, and sea stars can replace lost limbs; skates, rays, and sharks can regenerate kidneys; some kinds of worms can even grow into two new, separate individual worms if they're cut in half. Mammals, on the other hand, have very limited regeneration abilities. In humans, the only organ known to truly regenerate is the liver; young children also can sometimes crudely regenerate lost fingertips. But if you lose a limb, an eye, an ear, or any other part, you're out of luck.

The newt (a small, lizard-like aquatic amphibian) can regenerate lost body parts because as soon as it's injured, the remaining cells of the damaged tissue go back into the cell cycle: in short, they start dividing. In contrast, most of our cells are locked out of the cell cycle once they've differentiated, or taken a specific form like muscle or bone marrow. Scientists have looked to pluripotent stem cells, which have not yet taken on a specific role, as sources of new tissue. However, it's challenging to artificially coax these stem cells into exactly the kind of cell you want. The advantage of the newt's system is that it takes differentiated cells back just one step. The cells "know their identity," as Blau puts it, so you'll get muscle cells from muscle cells, and so on.

By blocking the function of just two proteins, called Rb and ARF, Blau's team was able to make mouse muscle cells regenerate like newt cells. However, the new muscle cells merged successfully with the old cells only if the researchers turned Rb back on. If they didn't, the new cells grew too much and interfered with the function of the old muscle cells. In other words, they became tumors. And in fact, the function of both Rb and ARF in mammals is to suppress the growth of tumors.

The research suggests that there's some kind of evolutionary trade-off between regeneration and cancer susceptibility, and the more complex the organism, the more risky regeneration becomes. So while many simpler life forms have been able to retain the ability to regenerate, we mammals haven't. However, Blau's work shows that we never really lost the potential to regenerate; our bodies just keep a tight lid on it.

The research could pave the way for exciting new therapies that allow us to replace lost limbs and other body parts. However, in order for such a therapy to work, scientists would have to figure out a way to do it safely, which would mean turning off the tumor suppressors for as little time as possible, in just one very specific location. Even then, the technique might not be safe. Time will tell if humans will ever be able to imitate the humble newt.

Now try and answer these questions:

What is the difference between regeneration and healing?

Why can newts regenerate lost limbs, but mammals can't?

How did the researchers induce regeneration in mouse muscle cells?

It's not clear why simpler animals are more likely to regenerate than more complex ones. What reasons can you imagine?

You may want to check out the August 20, 2010, Science Update Podcast to hear further information about this Science Update and the other programs for that week. This podcast's topics include: beating aphids at their own game, why some birds bob their tails, ancient terror birds of South America, and more.